Biology subjects

Adachi, A.

Publications and source records attributed to Adachi, A..

4 recordsLinked to original sources

bioRxiv2025

GPCR Antagonism via Antibody-Mediated Rewiring of Receptor Trafficking and Degradation

G-protein coupled receptors (GPCRs) represent one of the most important yet incompletely targeted classes of therapeutic proteins. Here, we report a novel strategy for functional GPCR antagonism through antibody-mediated endocytosis and lysosomal degradation. Our engineered bispecific antibodies, termed GPCR-TfR1 Targeting Chimeras (GTACs), achieve potent and selective downregulation of various GPCRs, including RXFP1 and CCR6, critical cancer and immune drug targets that are difficult to antagonize with conventional approaches. GTACs led to complete inhibition of receptor activity with over 100-fold greater potency than conventional antibody antagonists. Using four-color imaging, we elucidated the trafficking mechanism of both the target protein and TfR1 in living cells. The GTAC platform enables robust antagonism of signaling across diverse GPCR families and establishes induced endocytosis and lysosomal trafficking as a fundamentally new paradigm for therapeutic GPCR modulation.

bioengineering↗

bioRxiv2024

Soil nutrition-dependent dynamics of the root-associated microbiome in paddy rice

O_LIPlants accommodate diverse microbial communities (microbiomes), which can change dynamically during plant adaptation to varying environmental conditions. However, the direction of these changes and the underlying mechanisms driving them, particularly in crops adapting to the field conditions, remain poorly understood. C_LIO_LIWe investigate the root-associated microbiome of rice (Oryza sativa L.) using 16S rRNA gene amplicon and metagenome sequencing, across four consecutive cultivation seasons in a high-yield, non-fertilized, and pesticide-free paddy field, compared to a neighboring fertilized and pesticide-treated field. C_LIO_LIOur findings reveal that root microbial community shifts and diverges based on soil fertilization status and plant developmental stages. Notably, nitrogen-fixing bacteria such as Telmatospirillum, Bradyrhizobium and Rhizomicrobium were over-represented in rice grown in the non-fertilized field, implying that the assembly of these microbes supports rice adaptation to nutrient-deficient environments. C_LIO_LIA machine learning model trained on the microbiome data successfully predicted soil fertilization status, highlighting the potential of root microbiome analysis in forecasting soil nutrition levels. Additionally, we observed significant changes in the root microbiome of ccamk mutants, which lack a master regulator of mycorrhizal symbiosis, under laboratory conditions but not in the field, suggesting a condition-dependent role for CCaMK in establishing microbiomes in paddy rice. C_LI

plant biology↗

bioRxiv2021

A rise-to-threshold signal for a relative value deliberation

Whereas progress has been made in identifying neural signals related to rapid, cued decisions1-4, less is known about how brains guide and terminate more ethologically relevant deliberations, where an animals own behavior governs the options experienced over minutes5-8. Drosophila search for many seconds to minutes for egg-laying sites with high relative value9, 10 and neurons, called oviDNs, exist whose activity fulfills necessity and sufficiency criteria for initiating the egg-deposition motor program11. Here we show that oviDNs express a calcium signal that rises over seconds to minutes as a fly deliberates whether to lay an egg. The calcium signal dips when an egg is internally prepared (ovulated), rises at a rate related to the relative value of the current substrate being experienced, and reaches a consistent peak just prior to the abdomen bend for egg deposition. We provide perturbational evidence that the egg-deposition motor program is initiated once this signal hits a threshold and that sub-threshold variation in the signal regulates the time spent deliberating and, ultimately, the option chosen. These results argue that a rise-to-threshold signal guides Drosophila to lay eggs on substrate options with high relative value, with each egg-laying event representing a self-paced decision similar to real-world decisions made by humans and other mammals.

neuroscience↗

bioRxiv2018

Walking Drosophila aim to maintain a neural heading estimate at an internal goal angle

While navigating their environment, many animals track their angular heading via the activity of heading-sensitive neurons. How internal heading estimates are used to guide navigational behavior, however, remains largely unclear in any species. We found that normal synaptic output from heading neurons in Drosophila is required for flies to stably maintain their trajectory along an arbitrary direction while navigating a simple virtual environment. We further found that if the heading estimate carried by these neurons is experimentally redirected by focal stimulation, the fly typically turns so as to rotate this internal heading estimate back towards the initial angle, while also slowing down until this correction has been made. These experiments argue that flies compare an internal heading estimate with an internal goal angle to guide navigational decisions, highlighting an important computation underlying how a spatial variable in the brain is translated into navigational action.\n\nOne Sentence SummaryFlies compare an internal heading estimate with an internal goal angle to guide navigation.

neuroscience↗